Mincle receptor

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Macrophage inducible Ca2+-dependent lectin receptor, (abbreviated to Mincle), is a member of the C-type lectin superfamily encoded by the gene CLEC4E. It is a pattern recognition receptor that can recognize glycolipids including mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). [1] [2] The mincle receptor binds a range of carbohydrate structures, predominantly containing glucose or mannose, and play an important role in recognition of bacterial glycolipids by the immune system. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and Syk. Cord factor also binds and activates the related C-type lectin MCL. [3] [4] Upon receptor stimulation is PKC-δ activated, which subsequently phosphorylates CARD9 that triggers recruitment of BCL10 and MALT1, leading to a CARD-CC/BCL10/MALT1 (CBM) signaling complex. [5] This signaling complex in turn triggers downstream recruitment of TRAF6 and NF-κB activation.

Contents

A wide range of ligands promote signalling through Mincle, including proteins, sterols and glycolipids from altered or damaged self, and various glycolipids from pathogenic and commensal organisms.

Mincle agonists from self

Crystalline cholesterol, which accumulates in atherosclerotic lesions, can signal through human Mincle. [6] Cholesterol sulfate, which is present in the skin, is a cause of sterile inflammation through agonizing Mincle signalling. [7] The protein SAP130 signal through Mincle. [8] Beta-glucosylceramide, which accumulates as a result of the lysosomal storage disorder Gaucher’s disease, signals through Mincle. [9]

Mincle agonists from microbes

Mycobacteria and corynebacteria produce a wide range of glycolipids that can signal through Mincle. These include glucose and trehalose mycolates, and their closely related corynomycolates from mycobacteria and corynebacteria. [10] Glycosyl diglycerides from various pathogenic and commensal bacteria and fungi such as Lactobacillus plantarum, [11] Streptococcus pneumoniae, [12] [13] Mycobacterium tuberculosis [14] and Malassezia sp. [15]

See also

Related Research Articles

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<span class="mw-page-title-main">DC-SIGN</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CD23</span> Low-affinity" receptor for IgE

CD23, also known as Fc epsilon RII, or FcεRII, is the "low-affinity" receptor for IgE, an antibody isotype involved in allergy and resistance to parasites, and is important in regulation of IgE levels. Unlike many of the antibody receptors, CD23 is a C-type lectin. It is found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets.

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<span class="mw-page-title-main">KLRD1</span>

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<span class="mw-page-title-main">Interleukin-6 receptor</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">OLR1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CD69</span>

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<span class="mw-page-title-main">CLEC7A</span> Protein-coding gene in humans

C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

<span class="mw-page-title-main">KLRC4</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">KLRB1</span> Protein-coding gene in humans

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<span class="mw-page-title-main">KLRC2</span> Protein-coding gene in humans

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<span class="mw-page-title-main">Cord factor</span> Chemical compound

Cord factor, or trehalose dimycolate (TDM), is a glycolipid molecule found in the cell wall of Mycobacterium tuberculosis and similar species. It is the primary lipid found on the exterior of M. tuberculosis cells. Cord factor influences the arrangement of M. tuberculosis cells into long and slender formations, giving its name. Cord factor is virulent towards mammalian cells and critical for survival of M. tuberculosis in hosts, but not outside of hosts. Cord factor has been observed to influence immune responses, induce the formation of granulomas, and inhibit tumor growth. The antimycobacterial drug SQ109 is thought to inhibit TDM production levels and in this way disrupts its cell wall assembly.

<span class="mw-page-title-main">NKG2D</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Stimulator of interferon genes</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CLEC6A</span> Protein-coding gene in humans

Dectin-2 or C-type lectin domain containing 6A is a protein that in humans is encoded by the CLEC6A gene. Dectin-2 is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded protein is a type II transmembrane protein with an extracellular carbohydrate recognition domain. It functions as a pattern recognition receptor recognizing α-mannans and as such plays an important role in innate immune response to fungi. Expression is found on macrophages and dendritic cells. It can also be found at low levels in Langerhans cells and peripheral blood monocytes, where expression levels could be increased upon induction of inflammation.

<span class="mw-page-title-main">Paired receptors</span>

Paired receptors are pairs or clusters of receptor proteins that bind to extracellular ligands but have opposing activating and inhibitory signaling effects. Traditionally, paired receptors are defined as homologous pairs with similar extracellular domains and different cytoplasmic regions, whose genes are located together in the genome as part of the same gene cluster and which evolved through gene duplication. Homologous paired receptors often, but not always, have a shared ligand in common. More broadly, pairs of receptors have been identified that exhibit paired functional behavior - responding to a shared ligand with opposing intracellular signals - but are not closely homologous or co-located in the genome. Paired receptors are highly expressed in the cells of the immune system, especially natural killer (NK) and myeloid cells, and are involved in immune regulation.

References

  1. ↑ Moody, DB; Matsunaga, I (2009). "Mincle is a long sought receptor for mycobacterial cord factor". Journal of Experimental Medicine. 206 (13): 2879–88. doi:10.1084/jem.20092533. PMC   2806465 . PMID   20008525.
  2. ↑ Ishikawa, E; Ishikawa T; Morita YS; Toyonaga K; Yamada H; Takeuchi O; Kinoshita T; Akira S; Yoshikai Y; Yamasaki S (2009). "Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle". Journal of Experimental Medicine. 206 (13): 2865–8. doi:10.1084/jem.20091750. PMC   2806462 . PMID   20008526.
  3. ↑ Miyake, Y; Toyonaga K; Mori D; Kakuta S; Hoshino Y; Oyamada A; Yamada H; Ono K; Suyama M; Iwakura Y; Yoshikai Y; Yamasaki S (2013). "C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor". Immunity. 38 (5): 1050–1062. doi: 10.1016/j.immuni.2013.03.010 . PMID   23602766.
  4. ↑ Richardson, Mark B.; Williams, Spencer J. (2014-06-23). "MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns". Frontiers in Immunology. 5: 288. doi: 10.3389/fimmu.2014.00288 . ISSN   1664-3224. PMC   4066366 . PMID   25002863.
  5. ↑ Strasser D, Neumann K, Bergmann H, Marakalala MJ, Guler R, Rojowska A; et al. (2012). "Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity". Immunity. 36 (1): 32–42. doi:10.1016/j.immuni.2011.11.015. PMC   3477316 . PMID   22265677.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ↑ Kiyotake, R; Oh-Hora, M; Ishikawa, E; Miyamoto, T; Ishibashi, T; Yamasaki, S (16 October 2015). "Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses". The Journal of Biological Chemistry. 290 (42): 25322–32. doi: 10.1074/jbc.M115.645234 . PMC   4646182 . PMID   26296894.
  7. ↑ Kostarnoy, AV; Gancheva, PG; Lepenies, B; Tukhvatulin, AI; Dzharullaeva, AS; Polyakov, NB; Grumov, DA; Egorova, DA; Kulibin, AY; Bobrov, MA; Malolina, EA; Zykin, PA; Soloviev, AI; Riabenko, E; Maltseva, DV; Sakharov, DA; Tonevitsky, AG; Verkhovskaya, LV; Logunov, DY; Naroditsky, BS; Gintsburg, AL (28 March 2017). "Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate". Proceedings of the National Academy of Sciences of the United States of America. 114 (13): E2758–E2765. Bibcode:2017PNAS..114E2758K. doi: 10.1073/pnas.1611665114 . PMC   5380039 . PMID   28292894.
  8. ↑ Yamasaki, S; Ishikawa, E; Sakuma, M; Hara, H; Ogata, K; Saito, T (October 2008). "Mincle is an ITAM-coupled activating receptor that senses damaged cells". Nature Immunology. 9 (10): 1179–88. doi:10.1038/ni.1651. PMID   18776906. S2CID   205361789.
  9. ↑ Nagata, Masahiro; Izumi, Yoshihiro; Ishikawa, Eri; Kiyotake, Ryoko; Doi, Rieko; Iwai, Satoru; Omahdi, Zakaria; Yamaji, Toshiyuki; Miyamoto, Tomofumi (18 April 2017). "Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity". Proceedings of the National Academy of Sciences of the United States of America. 114 (16): E3285–E3294. Bibcode:2017PNAS..114E3285N. doi: 10.1073/pnas.1618133114 . ISSN   1091-6490. PMC   5402399 . PMID   28373578.
  10. ↑ van der Peet, PL; Gunawan, C; Torigoe, S; Yamasaki, S; Williams, Spencer J (2015). "Corynomycolic acid-containing glycolipids signal through the pattern recognition receptor Mincle". Chem. Commun. 51 (24): 5100–5103. doi:10.1039/c5cc00085h. PMID   25714652.
  11. ↑ Shah, S; Nagata M; Yamasaki D; Williams SJ (2016). "Total synthesis of a cyclopropane-fatty acid α-glucosyl diglyceride from Lactobacillus plantarum and identification of its ability to signal through Mincle". Chemical Communications. 52 (72): 10902–1065. doi:10.1039/C6CC05631H. PMID   27533919.
  12. ↑ Behler-Janbeck, F; Takano, T; Maus, R; Stolper, J; Jonigk, D; Tort Tarrés, M; Fuehner, T; Prasse, A; Welte, T; Timmer, MS; Stocker, BL; Nakanishi, Y; Miyamoto, T; Yamasaki, S; Maus, UA (December 2016). "C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia". PLOS Pathogens. 12 (12): e1006038. doi: 10.1371/journal.ppat.1006038 . PMC   5140071 . PMID   27923071.
  13. ↑ Imai, T; Matsumura, T; Mayer-Lambertz, S; Wells, CA; Ishikawa, E; Butcher, SK; Barnett, TC; Walker, MJ; Imamura, A; Ishida, H; Ikebe, T; Miyamoto, T; Ato, M; Ohga, S; Lepenies, B; van Sorge, NM; Yamasaki, S (6 November 2018). "Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection". Proceedings of the National Academy of Sciences of the United States of America. 115 (45): E10662–E10671. Bibcode:2018PNAS..11510662I. doi: 10.1073/pnas.1809100115 . PMC   6233082 . PMID   30352847.
  14. ↑ Richardson MB, S, S, SJ., MB; Torigoe, S; Yamasaki, S; Williams, SJ (2015). "Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides signal through the pattern recognition receptor Mincle: total synthesis and structure activity relationships". Chem. Commun. 51 (81): 15027–30. doi:10.1039/c5cc04773k. PMID   26310657.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ Ishikawa, T; Itoh, F; Yoshida, S; Saijo, S; Matsuzawa, T; Gonoi, T; Saito, T; Okawa, Y; Shibata, N; Miyamoto, T; Yamasaki, S (17 April 2013). "Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia". Cell Host & Microbe. 13 (4): 477–88. doi: 10.1016/j.chom.2013.03.008 . PMID   23601109.


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